1. Field of the Invention
The present invention relates to a process for preparing 2,2-difluoroethylamine of the formula (I) and salts thereof, for example sulphates, hydrochlorides or acetates, which proceeds from difluoroacetonitrile.
2. Description of Related Art
2,2-Difluoroethylamines and salts thereof are important intermediates for preparation of active ingredients, especially active agrochemical ingredients. Various preparation methods for 2,2-difluoroethylamine are known.
Donetti et al. (J. Med. Chem. 1989, 32, 957-961) describe, for example, the synthesis of 2,2-difluoroethylamine hydrochloride proceeding from 2,2-difluoroacetamide, in which the corresponding amide is reduced with a diboran solution in tetrahydrofuran (THF). Kluger et al. describe, in JACS 1982, 104, 10, 2891-2897, the reduction of 2,2-difluoroacetamide with sodium boranate and boron trifluoride etherate to give 2,2-difluoroethylamine.
The low yield and the use of expensive and hazardous chemicals, for example sodium boranate/BF3 or diborane, prevent the processes according to Donetti et al. and Kluger et al. from being suitable for the industrial scale preparation of 2,2-difluoroethylamine. All these processes are uneconomic, and industrial scale implementation is associated with high costs.
An inexpensive preparation process consists in the hydrogenation of difluoroacetonitrile, which is readily available as a starting material. It can be prepared, for example, from difluoroacetamide (Swarts et al., Bulletin des Societes Chimiques Belges 1922, 31, 364-5, Grunewald et al., J. Med. Chem. 2006, 49 (10), 2939-2952). The catalytic hydrogenation of trifluoroacetonitrile using PtO2 has been described by Gilman et al. (JACS 1943, 65 (8), 1458-1460), to obtain trifluoroethylamine hydrochloride.
The inventors have now found that the process described for trifluoroacetonitrile by Gilman et al. is unsuitable for the hydrogenation of difluoroacetonitrile. When the hydrogenation of difluoroacetonitrile is performed under the conditions described, 2,2-difluoroethylamine is obtained only in traces, whereas a multitude of more highly alkylated reaction products is otherwise obtained.
In addition, it has been found that the catalytic hydrogenation of difluoroacetonitrile in pure glacial acetic acid or in toluene does afford difluoroethylamine, but the conversions were unselective and the product was not isolable from the reaction mixture owing to the low boiling point.